Benzimidazole derivatives endowed with potent antileishmanial activity

摘要

Two sets of benzimidazole derivatives were synthesised and tested for activity against promastigotes of and . Most of the tested compounds resulted active against both species, with IC values in the low micromolar/sub-micromolar range. Among the set of 2-(long chain)alkyl benzimidazoles, whose heterocyclic head was quaternised, compound resulted about 100-/200-fold more potent than miltefosine, even if the selectivity index (SI) versus HMEC-1 cells was only moderately improved. In the set of 2-benzyl and 2-phenyl benzimidazoles, bearing a basic side chain in position 1, compound (2-(4-chlorobenzyl)-1-lupinyl-5-trifluoromethylbenzimidazole) was 12-/7-fold more potent than miltefosine, but exhibited a further improved SI. Therefore, compounds and represent interesting hit compounds, susceptible of structural modification to improve their safety profiles.